IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth

In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B...

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Autores principales:	Jiahui Li, Xiaolin Wu, Lars Schiffmann, Thomas MacVicar, Chenghui Zhou, Zhefang Wang, Dai Li, Oscar Velazquez Camacho, Reiner Heuchel, Margarete Odenthal, Axel Hillmer, Alexander Quaas, Yue Zhao, Christiane J. Bruns, Felix C. Popp
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pancreatic cancer tumor microenvironment IL17B/RB metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/10a86e8b578d436faf35403c549240bd
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spelling	oai:doaj.org-article:10a86e8b578d436faf35403c549240bd2021-11-11T15:28:41ZIL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth10.3390/cancers132153382072-6694https://doaj.org/article/10a86e8b578d436faf35403c549240bd2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5338https://doaj.org/toc/2072-6694In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.Jiahui LiXiaolin WuLars SchiffmannThomas MacVicarChenghui ZhouZhefang WangDai LiOscar Velazquez CamachoReiner HeuchelMargarete OdenthalAxel HillmerAlexander QuaasYue ZhaoChristiane J. BrunsFelix C. PoppMDPI AGarticlepancreatic cancertumor microenvironmentIL17B/RBmetabolismNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5338, p 5338 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic cancer tumor microenvironment IL17B/RB metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	pancreatic cancer tumor microenvironment IL17B/RB metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jiahui Li Xiaolin Wu Lars Schiffmann Thomas MacVicar Chenghui Zhou Zhefang Wang Dai Li Oscar Velazquez Camacho Reiner Heuchel Margarete Odenthal Axel Hillmer Alexander Quaas Yue Zhao Christiane J. Bruns Felix C. Popp IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
description	In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.
format	article
author	Jiahui Li Xiaolin Wu Lars Schiffmann Thomas MacVicar Chenghui Zhou Zhefang Wang Dai Li Oscar Velazquez Camacho Reiner Heuchel Margarete Odenthal Axel Hillmer Alexander Quaas Yue Zhao Christiane J. Bruns Felix C. Popp
author_facet	Jiahui Li Xiaolin Wu Lars Schiffmann Thomas MacVicar Chenghui Zhou Zhefang Wang Dai Li Oscar Velazquez Camacho Reiner Heuchel Margarete Odenthal Axel Hillmer Alexander Quaas Yue Zhao Christiane J. Bruns Felix C. Popp
author_sort	Jiahui Li
title	IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
title_short	IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
title_full	IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
title_fullStr	IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
title_full_unstemmed	IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
title_sort	il-17b/rb activation in pancreatic stellate cells promotes pancreatic cancer metabolism and growth
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/10a86e8b578d436faf35403c549240bd
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IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth

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